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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Richter, G; Gui, T; Bourgeois, B; Koyani, CN; Ulz, P; Heitzer, E; von, Lewinski, D; Burgering, BMT; Malle, E; Madl, T.
β-catenin regulates FOXP2 transcriptional activity via multiple binding sites.
FEBS J. 2021; 288(10):3261-3284 Doi: 10.1111/febs.15656 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Bourgeois Benjamin Michel Rene
Madl Tobias
Richter Gesa Lucia
Co-Autor*innen der Med Uni Graz
Heitzer Ellen
Koyani Chintan Navinchandra
Malle Ernst
Ulz Peter
von Lewinski Dirk

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The transcription factor forkhead box protein P2 (FOXP2) is a highly conserved key regulator of embryonal development. The molecular mechanisms of how FOXP2 regulates embryonal development, however, remain elusive. Using RNA sequencing, we identified the Wnt signaling pathway as key target of FOXP2-dependent transcriptional regulation. Using cell-based assays, we show that FOXP2 transcriptional activity is regulated by the Wnt coregulator β-catenin and that β-catenin contacts multiple regions within FOXP2. Using nuclear magnetic resonance spectroscopy, we uncovered the molecular details of these interactions. β-catenin contacts a disordered FOXP2 region with α-helical propensity via its folded armadillo domain, whereas the intrinsically disordered β-catenin N terminus and C terminus bind to the conserved FOXP2 DNA-binding domain. Using RNA sequencing, we confirmed that β-catenin indeed regulates transcriptional activity of FOXP2 and that the FOXP2 α-helical motif acts as a key regulatory element of FOXP2 transcriptional activity. Taken together, our findings provide first insight into novel regulatory interactions and help to understand the intricate mechanisms of FOXP2 function and (mis)-regulation in embryonal development and human diseases. DATABASE: Expression data are available in the GEO database under the accession number GSE138938.
Find related publications in this database (using NLM MeSH Indexing)
Amino Acid Sequence - administration & dosage
Animals - administration & dosage
Binding Sites - administration & dosage
Cell Line, Tumor - administration & dosage
Cloning, Molecular - administration & dosage
Embryo, Mammalian - administration & dosage
Escherichia coli - genetics, metabolism
Forkhead Transcription Factors - chemistry, genetics, metabolism
Gene Expression Profiling - administration & dosage
Gene Expression Regulation, Developmental - administration & dosage
Genetic Vectors - chemistry, metabolism
Humans - administration & dosage
Models, Molecular - administration & dosage
Osteoblasts - cytology, metabolism
Protein Binding - administration & dosage
Protein Conformation, alpha-Helical - administration & dosage
Protein Conformation, beta-Strand - administration & dosage
Protein Interaction Domains and Motifs - administration & dosage
Protein Isoforms - chemistry, genetics, metabolism
Recombinant Proteins - chemistry, genetics, metabolism
Sequence Alignment - administration & dosage
Sequence Homology, Amino Acid - administration & dosage
Transcription, Genetic - administration & dosage
Wnt Signaling Pathway - genetics
beta Catenin - chemistry, genetics, metabolism

Find related publications in this database (Keywords)
intrinsically disordered protein
signal transduction
transcriptional regulation
Wnt signaling
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